In Japan, the number of ovarian cancer patients is increasing year by year; the National Cancer Center (Japan) reports that 6742 people developed ovarian cancer in 1998, with annual fatalities also increasing to 4154 people in 2001. Advanced ovarian cancer at stages III-IV of the disease classification, is difficult to treat by surgery alone, and chemotherapy using anti-cancer agents is often performed. However, the prognosis for advanced ovarian cancer is poor, and figures from the National Cancer Center (Japan) for the year 2000 suggest the five-year survival rate for stage III ovarian cancer is 30%, while that of stage IV is as low as 12%. The development of novel therapeutic methods has thus been long awaited.
“Cell therapy” uses the cellular immune reactions of a living body based on scientific grounds (a point which distinguishes it from folk medicine using cells), and is a cancer therapy method that supplements surgery and chemotherapy (Non-Patent Document 1). One well-known example of “cell therapy” is “lymphocyte activated killer (LAK) therapy: adoptive immunotherapy”, developed by Rosenberg et al. in the 1980s (Non-Patent Document 2). In this method, blood comprising natural killer cells (NK cells) and T cells of a patient's blood is cultured in vitro, then the blood is returned into the veins of that same patient. For certain kinds of advanced cancer, adoptive immunotherapy has a definite effect; however, whether or not this therapeutic method achieves its tumor-reducing effect via a cancer antigen-specific immune reaction has been unclear, since the method does not limit the type of cancer cells. Therefore, for cellular therapies targeting malignant melanomas, a method wherein antigen-specific CD8-positive cytotoxic T cells are activated in vitro using peptides synthesized based on amino acid sequences of cancer antigens and returned to the body were selected and showed some effect. This method was beneficial in that it demonstrated that therapeutic strategies in which peptide-stimulated T cells reduce tumors in an antigen-specific manner were possible (Non-Patent Document 3).
However, there are several problems when it comes to applying this therapeutic method to other cancers, and the method has not yet been put to practical use. The following three problems have been mentioned: (1) time and labor are required in the conventional methods to determine cancer tumor-rejection antigens for each organ, and this is not easy; (2) it takes time to culture and obtain the necessary number of T cells; and (3) there is a high possibility that CD8-positive cytotoxic T cells by themselves have an established immunological tolerance (herein after called ‘tolerance’) to the cancer tumor-rejection antigen (Non-Patent Document 4).    [Non-Patent Document 1] Mitsuo Okubo, Cell therapy, pp. 948-957, Transfusion science revised 3rd edition, Hiroshi Tohyama et al., Chugai Igaku, Tokyo, 2004.    [Non-Patent Document 2] Rosenberg S A, Spiess P, Lafreiere R: A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocyte. Science. 233:1318-21, 1986.    [Non-Patent Document 3] Rosenberg S A, Yang J C, Schwartzentruber D J, et al.: Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Med. 4:321-327, 1998.    [Non-Patent Document 4] Mehrotra S, Stevens R, Zengou R, et al: Regulation of melanoma epitope-specific cytolytic T lymphocyte response by immature and activated dendritic cells, in vitro. Cancer Research. 63:5607-5614, 2003.